Analysis of altered function of dendritic cells from atopic dermatitis or psoriatic patients

特应性皮炎（AD）的特点是皮肤浸润和外周血中存在Th2型细胞，尽管在AD的慢性皮肤病变中也报道了干扰素-γ (IFN-γ)产生细胞的主要浸润。近年来，Th1或Th2的发育受到抗原提呈细胞（APCs）产生的因子的强烈影响。为了阐明AD患者APCs是否在Th2细胞分化中发挥有利作用，我们比较了13名AD患者和13名年龄匹配的健康对照者在不同试剂刺激后单核细胞（MOs）和单核细胞来源dc （MoDCs）细胞因子的产生和共刺激分子的表达。我们检测了它们IL-1β、IL-10、IL-12p40和IL-12p70的产生，以及CD23、CD40、CD54、CD80、CD83、CD86和HLA-DR的表达。我们用超抗原、LPS、激动性抗cd40抗体、植物血凝素（PHA）、IL-1β/TNF-α、IL-4或IFN-γ刺激它们。结果表明：1)LPS刺激后，AD MOs细胞IL-10的产生显著增加。相比之下，经过多种刺激后，AD MOs的IL-12p40产量明显低于HC MOs。2) LPS刺激后AD MoDCs中IL-12p40水平也显著降低。3) IL-4对CD23的诱导作用在AD MOs中显著升高。最后，4)抗cd40 Ab刺激后，AD MoDCs对CD83、CD86和HLA-DR表达的增强程度低于HC MoDCs。这些数据表明，在LPS、IL-1β/TNF-α、IL-4或抗cd40 Ab等刺激下，AD APCs表现出与HC APCs不同的反应，这些反应可能在AD患者识别的辅助性T细胞向Th2细胞极化过程中发挥作用。

Atopic dermatitis (AD) is characterized by the presence of Th2 type cells in the skin infiltration as well as in the peripheral blood, although a predominant infiltration of interferon-γ (IFN-γ)-producing cells is also reported in the chronic skin lesions of AD. Recently it has become clear that the development of Th1 or Th2 is strongly influenced by factors produced by the antigen presenting cells (APCs). To clarify whether APCs from AD patients play a favorable role in the differentiation of Th2 cells, we compared the production of cytokines and the expression of co-stimulatory molecules by monocytes (MOs) and monocyte-derived DCs (MoDCs) after stimulations with various reagents between 13 AD patients and 13 age-matched healthy controls. We examined their production of IL-1β, IL-10, IL-12p40, and IL-12p70, and their expression of CD23, CD40, CD54, CD80, CD83, CD86 and HLA-DR. We stimulated them with superantigens, LPS, agonistic anti-CD40 antibody, phytohemagglutinins (PHA), IL-1β/TNF-α, IL-4, or IFN-γ. The following results were obtained : 1) IL-10 production was significantly enhanced in AD MOs after LPS stimulation. In contrast, IL-12p40 production was significantly lower in AD MOs than in HC MOs after a variety of stimulations. 2) IL-12p40 was also significantly lower in AD MoDCs after LPS stimulation. 3) The induction of CD23 with IL-4 was significantly higher in AD MOs. And finally, 4) AD MoDCs augmented the expression of CD83, CD86, and HLA-DR less significantly than HC MoDCs after anti-CD40 Ab stimulation.These data indicate that AD APCs show some responses different from those observed in HC APCs after several stimulations, such as LPS, IL-1β/TNF-α, IL-4, or anti-CD40 Ab, and that these responses might play a role in the polarizing process of helper T cells into Th2 cells as recognized in AD patients.